Enhanced immunological response by dendritic cells in male hypogonadism.

Eur J Clin Invest 2012; 42 (11): 1205–1212 Abstract Background  The effect of male hypogonadism on the immune response is poorly understood, even though testosterone has both immunosuppressive and anti-inflammatory effects in men. Design  In this study, we compared the distribution and functional status of peripheral blood (PB) monocytes, dendritic cells (DCs) [CD16+ (monocytoid), CD33+ (myeloid) and CD33− (plasmacytoid)] and CD4+ CD25+ CD127−/lo regulatory T cells from hypogonadic men and control subjects. Immunophenotypic studies were performed both on resting and in vitro-stimulated cells. Results  Overall, no significant differences were detected on the number of monocytes, DCs and CD4+ CD25+ CD127−/lo regulatory T cells between both groups of subjects. However, hypogonadic men showed slightly higher numbers of circulating CD16+ cells expressing the CD107b activation/degranulation-associated marker than controls, such differences reaching statistical significance after in vitro stimulation with CpG oligodeoxynucleotides. Interestingly, antigen-stimulated expression of CD107b on CD16+ cells inversely correlated with the serum concentrations of total testosterone (r2 = −0·45; P = 0·01), free testosterone (r2 = −0·48; P = 0·005), calculated free testosterone (r2 = −0·44; P = 0·01) and bioavailable testosterone (r2 = −0·46; P = 0·008) among all cases studied, as well as with both the LH (r2 = −0·53, P = 0·04) and FSH (r2 = −0·54, P = 0·04) serum levels among hypogonadic men. Conclusions  These findings show an enhanced immunological response of circulating (activated) CD16+ DCs to antigen stimulation, which was inversely related to testosterone and gonadotropin serum levels. Such findings suggest a modulation by the hypothalamic–hypophyseal–gonadal axis of the immune response and may have clinical implications for hypogonadic men, as regards susceptibility to autoimmune diseases and increased responses to antigenic stimuli.